Hyaluronic acid is a non-sulfated glycosaminoglycan distributed throughout the body.

It is found in connective, epithelial and neural tissues.

The average 70KG adult has about 15 grams of hyaluronate in the body and approximately one third is degraded and replaced daily.

As part of the extracellular matrix, hyaluronic acid is a major component of synovial fluid. As such, HA increases the viscosity of the fluid. HA partners with lubricin, to be the major lubricators of a synovial joint.

Hyaluronic acid acts in the articular cartilage area, to coat the chondrocytes.

Aggrecan, also known as cartilage specific proteoglycan core protein, binds with hyaluronic acid and large aggregates are formed. These attract and hold water and are responsible for the resilience of cartilage. Resilience is defined as the resistance to compression.

Knee osteoarthritis is a slowly progressive joint disorder that affects 250 million people worldwide. It is characterized by joint pain, swelling, cartilage degradation and inflammation. It often causes impaired work performance and early retirement. The socioeconomic impact is vast. Currently, it is the third fastest rising diagnosis in the elderly population behind diabetes and dementia.

There are multiple treatment options for osteoarthritis of the knee. These range from conservative therapies and lifestyle modification to total knee replacement.

Common non-surgical options include non-steroidal anti-inflammatory drugs, physical therapy, analgesics and intra articular drugs such as steroids and hyaluronic acid.

Hyaluronic acid products have been used in the United States for treatment of osteoarthritis since 1997. They were approved by the Food and Drug Administration in 2005-2006. The initial mechanisms of action through which hyaluronic acid provides therapeutic effects include anti-inflammatory effects, chondroprotection, proteoglycan synthesis and shock absorbing properties. Studies have shown that patients with osteoarthritis have lost 50% or more of the hyaluronic acid in the affected joint space.

In 2013, the American Academy of Orthopedic Surgeons recommended against the use of hyaluronic acid for knee osteoarthritis. They claimed it did not work effectively. Since, many physician societies have recommended for the use of hyaluronic acid in patients with knee osteoarthritis. The American College of Rheumatology recommended HA for knee OA in patients who had an inadequate response to initial therapy. The European Society for Clinical and Economic Aspects of Osteoarthritis task force issued a consensus statement recommending the use of intra-articular hyaluronic acid in knee OA patients with mild to moderate disease and

for more severe patients who are not good candidates for total knee replacement surgery or wishing to delay the surgical procedure.

Despite the clinical considerations and availability of evidence recommending the use of hyaluronic acid in treating knee osteoarthritis, many remain skeptical. They site studies which show lack of efficacy. Perhaps, this is due to the patient selection or optimal treatment regimen.

In a 2017 review and meta-analysis, studies concerning the use of hyaluronic acid injections for osteoarthritis of the knee were examined. Primary outcome measure was the mean knee pain score at 13 weeks or 26 weeks. Secondary outcomes examined were the number of treatment related adverse events. Thirty articles were included and scrutinized.

Overall, 2-4 and greater than or equal to 5 injection regimens provided superior pain relief over controls. Single injections were not found to be more efficacious than saline. In fact, saline did better than single regimens of hyaluronic acid.

Intra-articular injections of HA used in a 2-4 injection treatment regimen provided the greatest benefit with respect to pain improvement in patients with osteoarthritis of the knee. Also, hyaluronic acid injections were found to be safe with few to no treatment related adverse events reported.

The significance of the superiority of the 2-4 regimen was only slightly better at the 3-month interval but the 5-injection subgroup demonstrated significant improvement in pain at the 6 month interval.

The authors of this analysis concluded that not only does the overall pooled estimate for hyaluronic acid as a class demonstrate a benefit for pain relief but there were differences in the results in the injection regimen provided.

The molecular weight of the hyaluronic acid product was examined. A wide range of molecular weights were reviewed and although higher weighted products did better, the single injection protocol did poorly when compared to the multiple dose treatments.

It has been suggested oxygen derived free radicals act as a mediator in the inflammatory response and that the radical species are responsible for hyaluronic acid degradation in the joint. Higher molecular weight products may achieve a better efficacy due to the increased residency time within the synovial fluid, producing a prolonged anti-inflammatory response within the joint, blocking inflammatory receptors, and a longer lasting inhibition of metalloproteinases, nitric oxide and the stimulation of proteoglycan synthesis which provide a chondroprotective effect.

Therefore, repeated exposures of HA may perpetuate improvement in the synovial fluid micro-environment allowing the HA shots to provide extended benefits. The authors concluded while molecular weight is an important factor, the number of injections plays a major role in optimizing the efficacy seen within knee osteoarthritis patients.

Even if a single injection of a high molecular weighted product was used, they did not demonstrate a reduction in pain comparable to the multi-injection groups.

Overall, 2-4 and greater than or equal to 5 injection regimens provided the best results at the 3 and 6 month follow ups and single dose treatments were no more efficacious than saline.

Integrative Practice Solutions has been using hyaluronic acid products in the treatment of knee osteoarthritis for greater than a decade and proud to state, we have never provided our patients with a single dose hyaluronic acid protocol.

Integrative Practice Solutions employs hyaluronic acid injections with guidance, unloading bracing and physical therapy to improve outcomes, well above the national average. Our patented Advanced Arthritis Relief Protocol™ (AARP) is now being used in many clinics across the United States with successful treatment outcomes in thousands of osteoarthritic patients and is approved by all major insurance programs including Medicare.

In conclusion, hyaluronic acid injections are an efficacious treatment modality for those with osteoarthritis of the knee when multiple doses are given.

Integrative Practice Solutions, through education, treatment protocols and newer technologies, is collaborating with the health care professional to increase treatment outcomes in this rapidly expanding population of osteoarthritic patients.

Regenerative Regards,

Dr. Robert McGrath